It is known that animal cells utilize .beta.-D-xylosides to prime glycosaminoglycan (GAG) synthesis. For example, p-nitrophenyl-.beta.-D-xyloside was shown to stimulate the synthesis of chondroitan sulfate in the mutant Chinese hamster ovary cells, pgsA-745 (Esko, J. et al., J Biol Chem (1988) 262:12189). In an Abstract recently published by Legumwa, F.N. et al., Glyconjugate J (1989) 6:457, it was reported that additional .beta.-D-xyloside conjugates, including those which include 1-octanyl, 1-hexadecanyl, cholesteryl, and farnesyl residues efficiently primed chondroitan sulfate synthesis in these cells. However, the 2-monooleyl glyceryl ether xyloside failed to prime the synthesis of any GAG in this system.
Chondroitan sulfate is only one of a group of GAGs, all of which are biosynthesized through the transfer of xylose units from UDP-xylose to specific serine residues in core proteins to obtain proteoglycans. The transfer of xylose units to the serine residues is followed by transfer of two galactose residues and one glucuronic acid residue to complete the formation of the linkage region tetrasaccharide D-GlcUA-.beta.1,3-D-Gal-.beta.1,3-D-Gal-.beta.1,4-D-Xyl-.beta.1,3-L-[Ser] common to chondroitan sulfate, dermatan sulfate, heparan sulfate and heparin. It appears that at least the first two transferases (xylosyl transferase and galactosyl transferase-I), act on core proteins regardless of their ultimate GAG composition. Synthetic .beta.-D-xylosides, however, appear to stimulate chondroitan sulfate synthesis preferentially.
Galactosyl transferase-I also transfers galactose to synthetic .beta.-D-xylosides to result in the formation of GAG chains (see, for example, Robinson, H.C. et al., Biochem J (1981) 194:575-586; Robinson, J.A. et al., Biochem J (1981) 194:839-846).
In general, the glycosamino glycans are alternating copolymers of a hexosamine and an alduronic acid which are found in sulfated forms. The members of the GAG family are classified by the nature of the hexosamine/alduronic acid repeating units. In chondroitan sulfates, the alduronic acid is primarily D-glucuronic acid and the hexosamine is acetylated 2-amino-2-deoxy-D-galactose (GalNAc). In heparin and heparan sulfate, the hexosamine is mostly acetylated and sulfated glucosamine (GlcNAc or GlcNS) and the alduronic acid is mostly L-iduronic in heparin and mostly D-glucuronic acid in heparan sulfate. It appears that heparan sulfate is convertible to heparin by conversion of the glucuronic acid residues to L-iduronic acid residues, which conversion involves a change in chirality at the 5C of the uronic acid residue.
Among the GAGs, heparan sulfate and heparin are particularly physiologically important as they are both anticoagulants and also antiproliferative with respect to smooth muscle cells. Thus, elevated levels of these GAGs are helpful in the context of preventing thrombosis and restinosis.